Publications

Category: Biologics and Biosimilars
Patel P, et al.

J Dermatolog Treat 2015;26(4):299-302.

Biological drugs are large, complex glycoprotein molecules produced in living organisms that have revolutionized the treatment of many conditions. As biologics used in several therapeutic areas will face patent expiration, this opens opportunities for competitive versions (biosimilars). As biologics are complex molecules they can never be replicated exactly; even innovator biologics have inherent batch-to-batch variability. When the second batch of innovator products were released, physicians began prescribing non-identical variants of biologics to their patients, accepting the possibility of variation in clinical effects. Unlike the variants in innovator products, biosimilars will provide clinical trial data demonstrating similar clinical effects, though there will always be some degree of uncertainty in how much clinical impact will be result from the variation in both innovator and biosimilar products.

Category: Biologics and Biosimilars
Chan JCN & Chan ATC

ESMO Open 2017;2(1):e000180.

Despite the high cost of development, due to their targeted nature with high efficacy, biologics are now taking on an increasingly important role in the treatment of common and/or serious diseases such as diabetes, cancer, chronic kidney disease, rheumatoid arthritis, psoriasis, blood disorders, vaccines and inflammatory bowel diseases. Unlike single molecules which are chemically synthesized with highly predictable structures and functions, biologics are pharmaceutical compounds synthesized or extracted from a biological source often with highly complex structures.

Category: Biologics and Biosimilars
Vezér B, Buzás Z, et al.

Curr Med Res Opin 2016;32(5):829-834.

This study investigated the number and types of manufacturing changes for originator monoclonal antibodies based on European Public Assessment Report documentation and ascertained the level of risk these changes might impart. The study highlighted EMA’s significant experience of process changes for originator monoclonal antibodies and the impact they may have on the efficacy and safety of biologicals. This experience is valuable for biosimilar product development.

Category: Biosimilars Concepts and the Totality of Evidence
Vulto AG and Jaquez A

Rheumatology (Oxford) 2017;56(suppl_4):iv14-iv29.

Biologic drugs are highly complex molecules and their key characteristics (known as critical quality attributes or CQAs) can vary based on posttranslational modifications that occur. The extent of variation in each CQA must be matched by biosimilar developers to the originator molecule to ensure biosimilarity. As analytical tools that measure differences at the molecular level are more sensitive and specific than tools that measure clinical differences, for example in clinical trials, biosimilar development has a greater focus on preclinical attributes, with phase 3 trials (if needed) being confirmatory. A well-controlled manufacturing process ensures that biosimilars consistently match the fingerprint of the originator molecule.

Category: Biosimilars Concepts and the Totality of Evidence
Declerck P, Rezk MF

Rheumatology (Oxford) 2017;56(suppl_4):iv4-iv13.

Similarity of biosimilars to originator molecules is established through a step-wise, comprehensive comparability exercise. This includes assessment of physicochemical, biological and immunochemical properties, in vivo pharmacology studies, phase 1 clinical studies (if appropriate) to determine pharmacokinetic and pharmacodynamic characteristics, and phase 3 clinical studies to determine the efficacy, safety profile and tolerability. Post-approval risk management is required and includes implementation of pharmacovigilance systems. The robust nature of this biosimilarity exercise is an important element when considering these agents.

Category: Biosimilars Concepts and the Totality of Evidence
Vanderkerckhove K., Seidl A. et al.

AAPS J 2018;20(4):68.

Regulatory agencies recommend biosimilars are assessed against their originator molecules in a stepwise fashion, starting with a detailed structural and functional analysis, followed by in vivo studies. If evidence from these analyses demonstrate similarity, this may justify a targeted clinical development plan. Therefore, careful design of the analytical phase of the process is critical.

Category: Biosimilars Concepts and the Totality of Evidence
European Commission

Consensus Information Paper 2013.

The European Commission has prepared this paper in order to provide payers, physicians and patients with adequate information on biosimilars. It gives a detailed overview of biologics and biosimilars, regulation and development of biosimilars, potential economic consequences of using biosimilars, as well as Q&A sections for each of the key stakeholders.

Category: Biosimilars Concepts and the Totality of Evidence
European Commission

Consensus Information Paper 2019.

Since the EU approved the first biosimilar medicine (‘biosimilar’) in 2006, the EU has pioneered the regulation of biosimilars. Over the past 10 years, the EU has approved the highest number of biosimilars worldwide, amassing considerable experience of their use and safety. This guide has been jointly developed by the EMA and European commission with the objective of providing healthcare professionals with reference information on both the science and regulation underpinning the use of biosimilars.

Category: Biosimilars Concepts and the Totality of Evidence
Wolff-Holz E, Tiitso K, et al

BioDrugs 2019;33(6):621-634.

The authors of this review focused on the nature and extent of clinical confirmation, in addition to analytical and functional data required by the European Medical Agency (EMA) for the approval of biosimilar products.

Category: Extrapolation
Weise M, Kurki P, et al.

Blood 2014;124(22):3191-3196.

This article addresses the concerns frequently raised in the medical community regarding the use of biosimilars in extrapolated indications and explains the underlying scientific and regulatory decision making, including some real-life examples from recently licensed biosimilars. This article is an extension to a paper published previously by Weise et al. (Blood 2012;120:5111–5117) which explained the principles of biosimilar development in general.

Category: Interchangeability
Kurki P, van Aerts L, et al.

BioDrugs 2017;31(2):83-91.

The introduction of biosimilars has shown that even complex proteins used for chronic disease treatment can be successfully copied. This in turn triggered discussions on aspects such as interchangeability between biosimilars and their reference products as well as the immunogenicity profiles of biosimilars.

Category: Interchangeability
Ebbers HC, Schellekens H.

Drug Discov Today. 2019;24(10):1963-1967.

Discussion about the interchangeability of biosimilars, where one medicine can be substituted for another without clinical consequence, persists. Biosimilars are approved based on a rigorous, step-wise comparability exercise demonstrating no clinically meaningful differences compared to the originator products. Furthermore, there are no data to suggest that the risk of immunogenicity is greater when switching to a biosimilar than when switching between different batches of the same originator biologic. The nocebo effect reinforces the need for physician involvement when switching but is not limited to biosimilars. For biosimilars to deliver on their promise, patients and physicians should be confident that they can be safely and effectively switched.

Category: Interchangeability
Kurki P, Barry S, et al.

Drugs. 2021;81(16):1881-1896.

This is a comprehensive analysis of prelicensing and postmarketing safety surveillance reports from the European Medicines Agency (EMA) of all biosimilar mAbs and fusion proteins approved before August 2020. The findings support the conclusion that EU-approved biosimilars are highly similar and interchangeable with their reference products, negating the need for additional systematic switch studies.

Category: Nocebo
Sharma A, Kumar N, et al.

Eye (Lond) 2020;34(6):1006-1007.

In this comment, authors describe the transformative effect of biologics in the treatment of diseases of the retina and the efforts to address patients’ non-compliance, driven by high-cost of biologics, through developing new biologics as well as biosimilars of already existing originators. Education around biosimilars for ophthalmologists needs to be revisited and topics such as nocebo addressed.

Category: Nocebo
Benedetti F, Piedimonte A.

Semin Arthritis Rheum. 2019;49(3S):S18-S21.

In this study, authors discuss the effects of language and psychosocial context on patients’ response to their treatment and course of disease.

Category: Nocebo
Kristensen LE, Alten R, et al.

BioDrugs 2018;32(5):397-404.

This review investigates the nocebo effect, defining the term and considering it in the process of switching from originator products to biosimilars. Three strategies aimed at mitigating the nocebo effect are discussed: positive framing, increasing patients and HCPs understanding of biosimilars and managed switching programs.

Category: Nocebo
Pouillon L, Danese S, et al.

Aliment Pharmacol Ther 2019;49(9):1181-1187.

The nocebo effect is under-recognised in the era of biosimilars, although it may negatively impact on the cost-savings of biosimilars. Future research should focus on the magnitude, the risk factors, the impact, and the management of the nocebo effect in biosimilars-treated IBD patients.

Category: Nocebo
Rezk MF and Pieper B.

Adv Ther 2018;35(6):749-753.

The authors take a closer look at the negative impact of the nocebo effect, as reported in a number of clinical trials, and its implications on patients’ perception when switching from an originator biologic to a biosimilar.

Category: Nocebo
Rezk MF and Pieper B.

Rheumatol Ther 2017;4(2):209-218.

The authors focus on the wide adoption of biosimilars, the re-emergence of the nocebo effect and the implications it may have on both patients and physicians’ perceptions as well as on treatment success. The authors also provide practical strategies and recommendations to raise awareness and to limit the nocebo effect.